MembersoftheTRPproteinfamilywerefirstidentifiedinDrosophila andwerefoundtobepartofthephototransductionprocessinDrosophila photoreceptors.Thusthename(TRP) referstothefactthatamutationinthegeneleadstoatransientdepolarizingresponsetoalightstimulusinsteadofthenormalsustainedresponse.Onthebasisofsequencehomology,anumberofgenesencodingTRPproteinshavebeenfoundinmammals(27inhumansalone),whicharecurrentlydividedintosevensubfamilies.TRPchannelsarecationpermeableandhaveastructuresimilartovoltage-gatedK+ channels.Theyarehomotetramersorheterotetramers.Eachsubunithassixtransmembranedomains.TRPproteinsappeartohaveavarietyoffunctions(e.g.,phototransduction,chemotransduction,andmechanotransduction)andareexpressedinanumberofcelltypes.Thoselistedin
Table7.1 appeartoactastemperaturesensorswithdistinctthermalsensitivitiesthatspantherangeofphysiologicallyrelevanttemperatures.
Modulation of the Transduction Process
As with the low-threshold mechanoreceptors for innocuous touch sensations, activation of the various nociceptor
Thefourthletterinthenameidentifiesthesubfamilyandwaschosenbecauseofthefirstmemberofthesubfamilyidentified:V,vanilloid;M,melastatin;A,ankyrin-like.Eachoftheproteinslistedisexpressedinatleastsomedorsalrootganglioncells,buttheyarealsoexpressedinothercelltypes.
CHAPTER 7 The Somatosensory System transduction proteins leads to a generator potential that causes spiking of the afferent, which transmits information to the CNS. In addition, activation of nociceptors also leads to local release of various chemical compounds, including tachykinins (substance P [SP]) and calcitonin gene–related protein (CGRP). These substances and others released from the damaged cells cause neurogenic inflammation (edema and redness of the surrounding skin).
In addition to causing a local reaction, these substances may serve to activate the insensitive or silent nociceptors mentioned earlier, such that they can henceforth respond to any subsequent damaging stimuli. Sensitization of silent nociceptors has been suggested to underlie allodynia (elicitation of painful sensations by stimuli that were innocuous before an injury) and hyperalgesia (increase in the level of pain felt to already painful stimuli). Thermal hyperalgesia is due to sensitization of TRPV1 channels. The Piezo2 current is increased by substances known to cause mechanical hyperalgesia and allodynia, suggesting changes in this current underlie these phenomena.
Centrifugal Control of Somatosensation
Sensory experience is not just the passive detection of environmental events. Instead, it more often depends on exploration of the environment. Tactile cues are sought by moving the hand over a surface. Visual cues result from scanning targets with the eyes. Thus sensory information is often received as a result of activity in the motor system. Furthermore, transmission in pathways to the sensory centers of the brain is regulated by descending control systems. These systems allow the brain to control its input by filtering the incoming sensory messages. Important information can be attended to and unimportant information can be ignored.
The tactile and proprioceptive somatosensory pathways are regulated by descending pathways that originate in the S-I and motor regions of the cerebral cortex. For example, cortical projections to the dorsal column nuclei help control the sensory input that is transmitted by the dorsal column– medial lemniscus pathway.